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Wednesday, April 7, 2010

Maternal Smoking in Pregnancy Linked to Increased Risk for Psychotic Symptoms in Adolescents

Pregnant? Please do not smoke! Your Baby's brain's at stake.

From Medscape Medical News Deborah Brauser

October 12, 2009 — The maternal use of tobacco while pregnant is associated with an increased risk for psychotic symptoms such as hallucinations and delusions in their children, with evidence of a dose-response effect, according to results from a large cohort study published in the October issue of the British Journal of Psychiatry.

"These findings indicate that the risk factors for development of non-clinical psychotic experiences may operate during early development," write Stanley Zammit, PhD, clinical senior lecturer in psychiatric epidemiology in the Department of Psychological Medicine at Cardiff University in Wales and the University of Bristol in the United Kingdom, and colleagues.

"This is the only study to really try and tease out to what extent this association is causal rather than being confounded or explained by other factors," Dr. Zammit told Medscape Psychiatry.

"There could still be confounding, of course, but this makes us a bit more confident that the association may be due to the effects of nicotine on the developing brain in the uterus," he added.

Smoking While Pregnant Common in the United Kingdom

"In the [United Kingdom], 15-20% of women continue to smoke throughout their pregnancy, and although cannabis use is less common, some alcohol intake during pregnancy is reported by most women," write the study authors.

They note that past studies have shown an association between maternal smoking and, to a lesser extent, maternal cannabis and alcohol use and adverse long-term effects on their offspring, including reduced cognitive ability and increased incidence of both attention-deficit/hyperactivity disorder and conduct disorder during childhood and adolescence.

However, the authors report that there have been very few epidemiological studies showing causal inference between maternal substance abuse and childhood psychopathology.

"Our aim [in this study] was to investigate, in a longitudinal design, whether maternal tobacco, cannabis, or alcohol use during pregnancy were independently associated with risk of the offspring developing psychotic symptoms during early adolescence," write the study authors.

"I'm interested in the effects of substance use on mental health outcomes," explained Dr. Zammit. "In animals, there is good evidence that nicotine in utero can disrupt the normal development/function of the fetal brain, so it seems very plausible that this could happen in humans and have subtle effects that are not noticeable early on in life but are only expressed later during development."

The investigators examined data from the Avon Longitudinal Study of Parents and Children, including 14,062 adolescents born between April 1991 and December 1992.

Dr. Zammit and his team focused their evaluation on a cohort of 6356 adolescents, all 12 years of age, who participated in a semistructured interview for psychosis-like symptoms (PLIKS). This interview included 12 core questions, which covered hallucinations, delusions, and experiences of thought interference during the past 6 months.

Data on parental substance use were obtained from self-report postal questionnaires completed by the mother at 8, 18, and 32 weeks of pregnancy and at 2, 21, 33, and 47 months after giving birth, and from the father at 18 weeks of pregnancy and at 2, 8, and 21 months after birth.

Of these mothers, 1219 (19.3%) smoked tobacco, 4372 (70.0%) drank alcohol, and 157 (2.5%) used cannabis at least once during pregnancy.

Maternal Tobacco Use Increased Risk for PLIKS

At the end of this cohort study, a total of 734 of the children (11.6%) were rated as having suspected or definite PLIKS, and 300 of these children (4.7%) had definite symptoms.

The investigators found that maternal tobacco use during pregnancy was strongly associated with an increased risk for suspected or definite PLIKS in their offspring (adjusted odds ratio [OR], 1.20; 95% confidence interval [CI], 1.05 – 1.37; P = .007). This risk further increased based on frequency of tobacco use.

In addition, "the offspring of mothers who used tobacco only in their third trimester had a greater risk of developing any suspected or definite PLIKS than offspring whose mothers smoked only in the first trimester (OR, 2.1; 95% CI, 0.96-4.59; P = 0.063)," report the authors.

After adjusting for confounders and maternal smoking during pregnancy, paternal smoking during pregnancy, maternal smoking postpregnancy, or maternal cannabis use were not associated with any suspected or definite PLIKS.

Although maternal alcohol use did show a nonlinear association with psychotic symptoms, this effect was found almost exclusively in the offspring of the 25 women who drank more than 21 units weekly.

Future Studies Needed

"Maternal smoking during pregnancy was associated with an increased risk of psychotic symptoms in the children, with evidence of a dose-response effect whereby risk of PLIKS was highest in the offspring of mothers who smoked most heavily," write the study authors.

"If our results are non-biased and truly reflect a causal relationship, we can estimate that about 20% of adolescents in this cohort would not have developed psychotic symptoms if their mothers had not smoked," they add.

Study limitations included missing data resulting from attrition and wave nonresponse, as well as possible underreporting of substance use (including cannabis, which is illegal in the United Kingdom).

"Hopefully this will encourage more research into the effects of tobacco on brain development in utero, and increase understanding of how any disruptions of brain development can impact risk of psychosis," Dr. Zammit concluded.

This study was supported by the Wellcome Trust Grant, with additional funding to Dr. Zammit through a Clinician Scientist Award from the National Assembly for Wales. The other study authors have disclosed no relevant financial relationships.

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